大麻素受体1在阻塞性睡眠呼吸暂停低通气综合征炎症反应中的神经免疫调节作用研究进展

The neuroimmunomodulatory effect of cannabinoid receptor 1 in the treatment of obstructive sleep apnea hypoventilation syndrome

阻塞性睡眠呼吸暂停低通气综合征(OSA)是一种全身性炎症性疾病,OSA病人睡眠结构的紊乱与下丘脑-垂体-肾上腺(HPA)轴的失调相互作用,持续激活HPA轴可诱导免疫细胞的糖皮质激素抵抗,使免疫系统反应转向促炎,导致并发症的加重,其特征性的慢性间歇低氧(CIH)也可通过多种途径激活糖皮质激素抑制核因子-κB(NF-κB)和相关炎症因子的表达,导致氧化应激、炎症、内皮功能障碍。内源性大麻素系统(ECS)在HPA轴活动以及对应激的神经内分泌反应中发挥主要调节作用,为机体提供重要的免疫防御。CIH可引起大麻素受体1(CB1R)表达增加,而CB1R拮抗剂可发挥抗炎作用,减轻CIH引起的器官损伤。CB1R拮抗剂已被证明可作为免疫抑制剂和抗炎剂,通过下调NF-κB信号发挥有益作用。现就CB1R拮抗剂调节OSA炎症反应潜在机制的研究进展进行综述。

Obstructive sleep apnea(OSA)is a systemic inflammatory disease,and disorder of sleep structure in patients with OSA is correlated with Hypothalamic-pituitary-adrenal axis(HPA),Dysregulated interaction of the HPA axis,continuous activation of the HPA axis can induce glucocorticoid resistance of immune cells,shifting the immune system response to proinflammatory,resulting in an aggravation of complications characterized by Chronic intermittent hypoxia,CIH(Chronic intermittent hypoxia)can also activate the expression of Nuclear factorκappa B(NF-κB)and related inflammatory factors through multiple pathways,leading to oxidative stress,inflammation,and endothelial dysfunction.The Endocannabinoid system(ECS)plays a major role in regulating the activity of HPA axis and neuroendocrine response to stress,providing an important immune defense for the body.CIH can induce increased expression of cannabinoid receptor 1(CB1R),and CB1R antagonists can play an anti-inflammatory role in reducing organ damage caused by CIH.CB1R antagonists have been shown to play a beneficial role as immunosuppressant and anti-inflammatory agent by down-regulating NF-κB signal.This overview reviews the research progress on the potential mechanism of CB1R antagonists in regulating OSA inflammatory response.